6-4 DIFFUSION–CONTROLLED REACTIONS AND BINDING MODES
Introduction

A diffusion–controlled reaction is one that occurs with every _______________ of the
reactants. Only a few chemical reactions can approach this rate, including
_______________ reactions, some _______________ transfers, and _______________
transfers.

The binding of a substrate to an enzyme is __________, so if the rest of the reaction is
simple and fast, the binding step may become the _____, which means the rxn may
approach the upper limit for catalysis.
Examples:

Triose Phosphate Isomerase – catalyzes the following reaction in the glycolysis and
gluconeogenesis pathways:

Its rate is so fast that it is close to the theoretical rate of a diffusion-controlled reaction.

Proposed mechanism:

Superoxide Dismutase
o Catalyzes the very rapid removal of the toxic superoxide radical anion (_____), a
by-product oxidative metabolism.
Overall reaction:
The mechanism involves a copper ion bound to the enzyme:
o Its rate is even faster than triose phosphate isomerase. It is even faster than what
is expected based on typical diffusion rates! This is accomplished by lining the
active site with positively-charged amino acid residues that guide the superoxide
radical anion to the copper ion bound at the bottom of the active site.
Binding Modes of Enzymatic Catalysis

Acid-base catalysis and covalent catalysis accelerate reactions by a factor of _____ to
_____, which is a small portion of the observed rate accelerations of enzymes (_____ to
_____).

The ability of proteins to specifically __________ and _______________ ligands
accounts for the remainder.

There are four types of binding modes:
1. Proximity effect – the correct _______________ of reacting groups in the active site.
2. Weak binding – If the substrate is bound too tightly, then mechanistic __________
may not occur. Weak binding _______________ reactions.
3. Induced fit – activation of an enzyme by a substrate-initiated _______________
change.
4. Transition–state stabilization – This increased interaction of the enzyme with the
substrate is considered the major factor in the _______________ of enzyme catalysis.
a. The “lock-and-key” concept is that enzymes are specific to the
_______________ __________, not the original substrate.